Gbp3 is associated with the progression of lupus nephritis by regulating cell proliferation, inflammation and pyroptosis

Abstract

Lupus nephritis (LN) is a major cause death in patients with systemic lupus erythematosus. We aimed to find the differentially expressed genes (DEGs) in LN and confirm the regulatory mechanism on LN. The mouse model of LN was constructed by subcutaneous injection of pristane. RNA-seq screened 392 up-regulated and 447 down-regulated DEGs in LN mouse model, and KEGG analysis found that the top 20 DEGs were enriched in arachidonic acid metabolism, tryptophan metabolism, etc. The hub genes, Kynu, Spidr, Gbp3, Cbr1, Cyp4b1, and Cndp2 were identified, in which Gbp3 was selected for following study. Afterwards, the function of Gbp3 on the proliferation, inflammation, and pyroptosis of LN was verified by CCK-8, ELISA, and WB in vitro. The results demonstrated that si-Gbp3 promoted cell proliferation and inhibited the levels of inflammatory factors (IL-1β, TNF-α and IL-8) and pyroptosis-related proteins (GSDMD, Caspase-1 and NLRP3) in a cell model of LN. In constrast, Gbp3 overexpression played an opposite role. In summary, Gbp3 promoted the progression of LN via inhibiting cell proliferation and facilitating inflammation and pyroptosis.

Keywords:

• transcriptome sequencing
• Gbp3
• pyroptosis

Authors' contributions

Zhongfeng Zhang conceived and designed the present study.

Wenyu Song and Run Yan performed the experiments, analysed the data, and drafted the article.

Zhongfeng Zhang revised the article critically for important intellectual content.

All authors read and approved the final manuscript.

Ethics approval and Patient consent

This study adhered to the tenets of the Declaration of Helsinki and was approved by the ethics committee of The Affiliated Hospital of Guizhou Medical University. The animal experiments were approved by the ethics committee of The Affiliated Hospital of Guizhou Medical University. All methods were carried out in accordance with relevant guidelines and regulations. All methods are reported in accordance with ARRIVE guidelines.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets generated and/or analysed during the current study are available in the [Run Yan] repository, [http://www.ncbi.nlm.nih.gov/bioproject/926917].

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.